The antiinflammatory properties of ivermectin and brimonidine in the treatment of papulopustular rosacea
Stein Gold LF, Lain EL, Harvey A. The antiinflammatory properties of ivermectin and brimonidine in the treatment of papulopustular rosacea. J Am Acad Dermatol 2018; 79(3):AB281-AB281.
J Am Acad Dermatol
Introduction: The pathophysiology of papulopustular rosacea (PPR) is not fully understood; however, there is increasing evidence that immune and inflammatory responses play an important role in the persistent and perilesional erythema of PPR. Multiple trials have demonstrated the efficacy of ivermectin 1% cream (IVM) and brimonidine 0.33% gel (BR) for treatment of the inflammatory lesions and erythema of PPR, respectively. Two recent studies suggest a promising synergy between IVM and BR in PPR.
Methods: In mice, ear edema was induced via topical TPA 0.01%, followed by topical vehicle, IVM (0.1% to 1%), or BR 0.2%. Ear thickness (μm) was measured using a micrometer. In human subjects, in a multicenter, randomized, double-blind, vehicle-controlled study of moderate/severe rosacea (Investigator Global Assessment [IGA] ≥3) patients were treated with once-daily: 1. BR (morning) and IVM (evening), 12 weeks (IVM+BR/12W; n = 49); 2. BR vehicle and IVM, 4 weeks, followed by BR and IVM, 8 weeks (IVM+BR/8W; n = 46); 3. BR vehicle and IVM vehicle, 12 weeks (n = 95). Assessments included IGA (0-4), Clinician’s Erythema Assessment (CEA; 0-4), and inflammatory lesion count. Adverse events (AEs) were monitored throughout the study.
Results: In the mouse, IVM treatment inhibited TPA induced skin inflammation in a dose dependent manner, and combination treatment using topical IVM and BR further reduced ear edema. Clinically, IVM+BR showed superior efficacy in all subgroups, with the greatest efficacy seen in the IVM+BR/12W group vs. vehicle (IGA success [clear/almost clear], 61.2% vs. 36.8%; P = .003). Eight treatment-related AEs in 6 subjects (3.2%) were reported (including treatment-related worsening of rosacea: 1 with IVM+BR [subject 8090-116], 3 with vehicle).
Summary: Adding BR to IVM treatment reduced inflammation in vivo, and demonstrated good efficacy and safety clinically. This treatment combination may improve treatment success without impairing tolerability.